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Sung-Won Kim

Publications and source records attributed to Sung-Won Kim.

33 records · Page 2Linked to original sources
PubMed2004

Development of early neutropenic fever, with or without bacterial infection, is still a significant complication after reduced-intensity stem cell transplantation.

Little information is available on the clinical characteristics of infectious complications that occur in the early period after reduced-intensity stem cell transplantation (RIST). We retrospectively investigated the clinical features of neutropenic fever and infectious episodes within 30 days after RIST in 76 patients who had received fluoroquinolones as part of their antibacterial prophylaxis. Preparative regimens included cladribine 0.66 mg/kg or fludarabine 180 mg/m2 plus busulfan 8 mg/kg. All but 1 patient survived 30 days after transplantation, and 75 patients (99%) became neutropenic within a median duration of 9 days. Neutropenic fever was observed in 29 patients (38%), and bacterial infection was confirmed in 15 (20%) of these, including bacteremia (n = 13), bacteremia plus pneumonia (n = 1), and urinary tract infection (n = 1). The causative organisms were gram-positive (n = 9) and gram-negative organisms (n = 7), with a mortality rate of 6%. Neither viral nor fungal infection was documented. Multivariate analysis showed that the presence of neutropenia at the initiation of preparative regimens was an independent risk factor for subsequent documented bacterial infections (P =.026; 95% confidence interval, 1.25-35.1). We conclude that neutropenic fever and bacteremia remain common complications in RIST.

Adolescent↗
PubMed2004

Early central nervous system complications after reduced-intensity stem cell transplantation.

To investigate clinical characteristics of early central nervous system (CNS) complications after reduced-intensity stem cell transplantation (RIST), we reviewed the medical records of 232 patients who had undergone RIST for hematologic diseases at our institutions between September 1999 and June 2003. All patients had received purine analog-based preparative regimens. Stem cell sources comprised granulocyte colony-stimulating factor-mobilized blood from HLA-identical or 1 locus-mismatched related donors (n = 151), unrelated bone marrow (n = 44), or unrelated cord blood (n = 37). Graft-versus-host disease prophylaxis incorporated cyclosporine with or without methotrexate. Diagnosis of CNS complications was based on clinical, radiologic, and microbiological findings. CNS complications occurred in 18 patients (7.8%), with a median onset of 22 days, and were infectious (n = 1), metabolic (n = 15), or cerebrovascular (n = 2). Symptoms included seizures (n = 7), visual disturbance (n = 2), headache (n = 8), nausea (n = 8), vomiting (n = 6), impaired consciousness (n = 16), and hemiparesis (n = 3). Complications improved promptly in 10 patients, and 8 patients died without improvement within 30 days. Multivariate analysis with logistic regression identified umbilical cord blood transplantation as a significant risk factor for early CNS complications (odds ratio, 14.5; 95% confidence interval, 3.7-56.9; P <.0001). CNS complications are a significant problem after RIST, particularly with umbilical cord blood. Limbic encephalopathy is an unrecognized subtype of neurotoxicity after umbilical cord blood transplantation.

Adult↗
PubMed2004

Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA-identical relative was identified for 12 patients. Nine patients underwent RIST. The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66 mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs-host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients achieved engraftment without grade III to IV nonhematologic regimen-related toxicity. All patients achieved complete donor-type chimerism without donor lymphocyte infusion by day 60. Four patients developed acute GVHD, and four developed chronic GVHD. One patient (11%) achieved partial response. As of July 2003, six patients were alive at median follow-up of 681 days. The actuarial overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival rate tended to be higher in the 12 patients with a matched donor than in the other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST procedure is feasible without severe toxicity. The efficacy of RIST for RCC should be confirmed in phase II/III clinical trials.

Acute Disease↗
PubMed2004

Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma.

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.

Acute Disease↗
PubMed2004

Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

Chronic Disease↗
PubMed2004

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients.

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.

Acute Disease↗
PubMed2003

Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

Anticoagulants↗
PubMed2003

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗
PubMed2003

Feasibility of acute physiology and chronic health evaluation (APACHE) II and III score-based screening in patients receiving allogeneic hematopoietic stem-cell transplantation.

Patients who require management in the intensive care unit (ICU) for complications after allogeneic hematopoietic stem-cell transplantation (HSCT) generally have a poor outcome. We retrospectively studied whether the risk-prediction stratification systems commonly used for patients admitted to the ICU, that is, the Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III systems, could be useful for identifying patients who should receive intensive care earlier. We reviewed the medical records of 210 patients who underwent allogeneic HSCT and found that 18 (8.6%) had been admitted to the ICU for acute respiratory failure (n=9), acute renal failure (n=7), and septic shock (n=2). The median APACHE II and III scores were, respectively, 16 (10-27) and 55 (22-87) at the onset of complications and 26 (15-43) and 101 (65-157) upon admission to the ICU. Thus, both the APACHE II and APACHE III scores at ICU admission were higher than those at the onset of complications (P <0.0001). Seventeen patients (94%) subsequently died, with a median ICU stay of 7.5 days (1-51 days), as a result of multiorgan failure (n=14), respiratory failure (n=2), and septic shock (n=1). The APACHE II and III scores of the sole surviving patient were, respectively, 21 and 71 at the onset and 24 and 86 upon transfer to the ICU. Thus, the APACHE scores in this study were lower than those reported for other surgical or medical patients treated in the ICU, despite their uniform poor prognosis. Although nine patients had developed grade III to IV acute graft-versus-host disease, which is the most common cause of morbidity and mortality after allogeneic HSCT, this was not fully evaluated in the current scoring systems. Application of these systems to HSCT will require adequate modification, with particular attention to organ dysfunction secondary to graft-versus-host disease.

APACHE↗
PubMed2003

TRALI after the infusion of marrow cells in a patient with acute lymphoblastic leukemia.

BACKGROUND: TRALI is one of the most serious, life-threatening complications after blood transfusion. Antibodies against neutrophils or HLA molecules from the donor are thought to be the primary causative agents. Rarely, antibodies in the recipient may react with transfused neutrophils and initiate the same events, which raises the possibility that TRALI may also occur in an allogeneic PBPC transplantation setting. CASE REPORT: A 30-year-old Japanese man with acute lymphoblastic leukemia developed TRALI immediately after the infusion of marrow cells from an unrelated donor. The infusion was suspended, and he gradually improved after receiving steroids and oxygen support. The next day, the remaining cells, which were separated to MNCs, were infused with no reactions. He then recovered over 5 days without the use of mechanical ventilation. RESULTS: Laboratory evaluation disclosed the presence of antibodies to neutrophils in his sera sampled after transplantation, but not in the donor's marrow graft. Hence, antibodies to neutrophils in the recipient may have reacted with neutrophils in the graft and contributed to the development of TRALI. CONCLUSION: This is the first reported case of TRALI after allogeneic BMT. TRALI should be recognized as a rare but serious complication in allogeneic hematopoietic stem cell transplantation.

Acute Disease↗
PubMed2003

[Mini-transplantation for solid tumors].

With the hypothesis that RIST might be useful to induce immunological antitumor effect without excessive toxicities, we evaluated 27 patients(median age 38 years, range 4-59) with refractory non-renal solid tumors, who underwent RIST from the family donors. The primary and secondary endpoints included achievement of complete chimerism, and exploratory evaluation of graft-versus-tumor(GVT) effect, respectively. The conditioning regimen comprised purine analogue and busulfan with or without antithymocyte globulin. All patients achieved complete donor chimerism. These data demonstrate that RIST is a sufficient way to induce immune competent cells to patients with solid tumors. Although cases experienced probable GVT effect were observed in selective patients, total benefit for each tumor should be carefully evaluated in specific phase II-III trials.

Adolescent↗
PubMed2002

Identification of angiogenesis in primary breast carcinoma according to the image analysis.

Tumor angiogenesis may be an independent prognostic factor for breast cancer survival. However, we can get the angiogenic property of the breast cancer only after the removal of breast tissue. To get this information before surgical resection of the tumor, we evaluated 29 breast carcinoma patients with Tc-99m MIBI scintimammography and power Doppler ultrasound (US) with a microbubble contrast agent preoperatively and compare their results with intratumoral microvessel density (IMD) and reverse transcriptase-polymerase chain reaction (RT-PCR) of VEGF mRNA. IMD was well correlated with VEGF121 (r = 0.220, P = 0.024) and VEGF165 (r = 0.419, P = 0.046) mRNA level of the tumor. Power Doppler US grading of the tumor is well correlated with IMD (r = 0.552, P = 0.033). However, early uptake and washout index calculated from Tc-99m MIBI scintimammography showed no correlation with IMD or VEGF mRNA level, while washout index was inversely correlated with power Doppler US grading (r = -0.945, P = 0.001). In conclusion, the preoperative evaluation of breast cancer with power Doppler US with a microbubble contrast agent could predict tumor angiogenesis. Tc-99m MIBI scintimammography needs further study to use it as an image analysis for angiogenesis.

Adult↗
PubMedDate not supplied

Effect of estrogen, tamoxifen and epidermal growth factor on the transcriptional regulation of vascular endothelial growth factor in breast cancer cells.

BACKGROUND: VEGF (Vascular Endothelial Growth Factor) is a key factor of angiogenesis and high tissue VEGF levels are related to a poor prognosis in breast cancer. MATERIALS AND METHODS: By semi-quantitative RT-PCR, we determined the relative expressions of VEGF mRNA in MCF-7 (both ER-alpha+ and ER-beta+ (mainly ER-alpha+), PR+, bcl-2+, EGFR-) and MB-MDA-231 (only ER-beta+, PR-, EGFR-) breast cancer cells which were treated with estrogen, tamoxifen and EGF (Epidermal Growth Factor). RESULTS: In MCF-7 cell lines, estrogen induced the expression of VEGF mRNA while tamoxifen reduced its expression. Estrogen and tamoxifen did not confer any significant effect on MB-MDA-231 cells and EGF showed no significant effect on MCF-7 or MB-MDA-231. CONCLUSION: Reduced VEGF mRNA expression of MCF-7 cells treated with tamoxifen may be related to the antagonistic effect of tamoxifen on ER-positive breast cancer, and this antagonistic effect may be related to ER-alpha.

Breast Neoplasms↗